{"Name":"Hyperphenylalaninemia due to tetrahydrobiopterin deficiency","DiseaseID__c":"GARD:0007751","id":7751,"encodedName":"hyperphenylalaninemia-due-to-tetrahydrobiopterin-deficiency","IsDeleted":false,"Disease_Name_Full__c":"Hyperphenylalaninemia due to tetrahydrobiopterin deficiency","Xref_IDs__c":"68528007; C0751436; MEDGEN:199656; MONDO:0016543; ORPHA:238583","USA_Estimate__c":"5,000","No_of_Specialist_Tagsa__c":3,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":1,"World_Estimate__c":"8,000 to 80,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":1,"No_of_Disease_Descriptions__c":5,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":2,"Description_Source__c":"MONDO:0016543","Disease_Description__c":"A disorder of pterin metabolism characterized by tetrahydropterin (BH4) biosynthesis or recycling deficiencies, leading to central dopamine and serotonin deficiency, characterized by infantile-onset neurological disease of variable severity ranging from mild forms with minor neurological development to severe forms with hypotonia, developmental delay, complex movement disorder dominated by dystonia or dystonia parkinsonism.","GARD_Name__c":"Hyperphenylalaninemia due to tetrahydrobiopterin deficiency","GARD_Synonym__c":"bh4-deficient hyperphenylalaninemia; deficiency of tetrahydrobiopterin; hyperphenylalaninemia due to bh4 (tetrahydrobiopterin) deficiency; hyperphenylalaninemia due to bh4 deficiency; non-phenylketonuric hyperphenylalaninemia; tetrahydrobiopterin deficiency; tetrahydrobiopterin synthesis defect","Curated_Disease_Description_Source__c":"GARD:0007751","Curated_Disease_Description__c":"Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency.  This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"5,000","Age_at_Onset_Snippet_Text__c":"as a Newborn and as an Infant","SourceID__c":"ORPHA:238583","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Grouping","MONDO_ID__c":"MONDO:0016543","ORPHANET_ID__c":"ORPHA:238583","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Hiperfenilalaninemia por deficiencia de tetrahidrobiopterina","Spanish_Description_Source__c":"ORPHA:238583","Spanish_Description__c":"Es un trastorno del metabolismo de la pterina caracterizado por deficiencias de la biosíntesis o del reciclaje de tetrahidrobiopterina (BH4), que conduce a una deficiencia central de dopamina y serotonina. Está caracterizado por una enfermedad neurológica de inicio infantil de gravedad variable que va desde discreta afectación neurológica hasta formas graves con hipotonía y retraso del desarrollo, trastorno complejo del movimiento dominado por distonía o distonía-parkinsonismo.","Spanish_Disease_Name__c":"hiperfenilalaninemia por deficiencia de tetrahidrobiopterina","Spanish_GARD_Synonym__c":"hiperfenilalaninemia no fenilcetonúrica; hiperfenilalaninemia por deficiencia de bh4","Category_Linearization__c":"ORPHA:68367","icd10_id__c":null,"mesh_id__c":null,"omim_id__c":null,"snomed_id__c":null,"umls_id__c":null,"GARD_Disease__c":[{"Curated_Disease_Description__c":"Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency.  This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature.","Curated_Disease_Description_Source__c":"GARD:0007751","GARD_Synonym__c":"bh4-deficient hyperphenylalaninemia; deficiency of tetrahydrobiopterin; hyperphenylalaninemia due to bh4 (tetrahydrobiopterin) deficiency; hyperphenylalaninemia due to bh4 deficiency; non-phenylketonuric hyperphenylalaninemia; tetrahydrobiopterin deficiency; tetrahydrobiopterin synthesis defect","Name":"Hyperphenylalaninemia due to tetrahydrobiopterin deficiency","Curated_USA_Estimate__c":"5,000","estimateUsa":"5,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Metabolic Support UK","Website__c":"https://www.metabolicsupportuk.org"},{"Account_Name__c":"Pediatric Neurotransmitter Disease Association","Website__c":"https://www.pndassoc.org/"}],"GARD_Disease_Tag__c":[{"Tag_Name__c":"Genetics","Tag_Category__c":"Cause;Disease Category;Specialist","category_description":"Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.","curated_tag_name":"Genetic diseases"},{"Tag_Name__c":"Neurology","Tag_Category__c":"Disease Category;Specialist","category_description":"Neurological diseases affect the brain, spinal cord, cranial nerves, autonomic nerves, or other peripheral nerves.","curated_tag_name":"Neurological diseases"},{"Tag_Name__c":"Inborn Errors of Metabolism","Tag_Category__c":"Cause;Disease Category","category_description":"Inherited metabolic diseases, or inborn errors of metabolism, are a group of genetic diseases that affect the ability of the body's cells to convert food into energy.","curated_tag_name":"Inherited metabolic diseases"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:238583"},{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:238583"}],"Diagnosis__c":[{"Type__c":"NEWBORN","Category__c":"Secondary","Curie__c":"http://newbornscreeningcodes.nlm.nih.gov/nb/sc/condition/BIOPT-REG"},{"Type__c":"NEWBORN","Category__c":"Secondary","Curie__c":"http://newbornscreeningcodes.nlm.nih.gov/nb/sc/condition/BIOPT-BS"},{"Type__c":"GTR","Curie__c":"MEDGEN:C0751435"},{"Type__c":"GTR","Curie__c":"MEDGEN:C0751436"}],"External_Identifier_Disease__c":[{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C0751436","Source__c":"C0751436","Xref__c":"C0751436"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=68528007","Source__c":"MONDO:0016543","Xref__c":"68528007"},{"URL__c":"https://www.orpha.net/en/disease/detail/238583","Source__c":"C0751436; MONDO:0016543; ORPHA:238583","Xref__c":"ORPHA:238583"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=199656","Source__c":"C0751436","Xref__c":"MEDGEN:199656"},{"URL__c":"https://medlineplus.gov/genetics/condition/tetrahydrobiopterin-deficiency","Source__c":"GARD:0007751","Xref__c":"https://medlineplus.gov/genetics/condition/tetrahydrobiopterin-deficiency"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=68724006","Source__c":"C0751436","Xref__c":"68724006"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0016543","Source__c":"GARD:0007751","Xref__c":"MONDO:0016543"}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Decreased concentration of homovanillic acid (HVA) in the cerebrospinal fluid. HVA is a metabolite of dopamine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003785","HPO_Name__c":"Decreased CSF homovanillic acid concentration","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A deviation from the normal concentration of biopterin in the blood circulation.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0040210","HPO_Name__c":"Abnormal circulating biopterin concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000708","HPO_Synonym__c":"Behavioral abnormality; Behavioral changes; Behavioral disorders; Behavioral disturbances; Behavioral problems; Behavioral symptoms; Behavioral/psychiatric abnormalities; Behavioural symptoms; Behavioural/Psychiatric abnormality; Psychiatric disorders; Psychiatric disturbances","HPO_Name__c":"Atypical behavior","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001250","HPO_Synonym__c":"Epileptic seizure; Seizures","HPO_Name__c":"Seizure","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increased concentration of L-phenylalanine in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0004923","HPO_Name__c":"Hyperphenylalaninemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001276","HPO_Synonym__c":"Hypertonicity; Increased muscle tone","HPO_Name__c":"Hypertonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormally increased amount of 7-biopterin in the urine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0033594","HPO_Synonym__c":"Primapterinuria","HPO_Name__c":"Elevated urinary 7-biopterin level","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002421","HPO_Synonym__c":"Delay in head control; Delay in head righting; Infant head lag; Poor head control","HPO_Name__c":"Poor head control","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100543","HPO_Synonym__c":"Abnormality of cognition; Cognitive abnormality; Cognitive defects; Cognitive deficits; Cognitive impairment; Intellectual impairment","HPO_Name__c":"Cognitive impairment","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012758","HPO_Synonym__c":"NDD","HPO_Name__c":"Neurodevelopmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The term Maturity-onset diabetes of the young (MODY) was initially used for patients diagnosed with fasting hyperglycemia that could be treated without insulin for more than two years, where the initial diagnosis was made at a young age (under 25 years). Thus, MODY combines characteristics of type 1 diabetes (young age at diagnosis) and type 2 diabetes (less insulin dependence than type 1 diabetes). The term MODY is now most often used to refer to a group of monogenic diseases with these characteristics. Here, the term is used to describe hyperglycemia diagnosed at a young age with no or minor insulin dependency, no evidence of insulin resistance, and lack of evidence of autoimmune destruction of the beta cells.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0004904","HPO_Synonym__c":"Maturity onset diabetes of the young","HPO_Name__c":"Maturity-onset diabetes of the young","Feature_System__c":"Endocrine System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001300","HPO_Name__c":"Parkinsonism","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Any deviation from the normal concentration of neopterin in the blood circulation.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0040206","HPO_Name__c":"Abnormal circulating neopterin concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormally decreased magnesium concentration in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002917","HPO_Synonym__c":"Low blood magnesium levels; Low blood Mg levels","HPO_Name__c":"Hypomagnesemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormal pattern in the quality, quantity, or characteristics of sleep.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002360","HPO_Synonym__c":"Difficulty sleeping; Sleep abnormality; Sleep disturbances; Sleep dysfunction; Sleep-wake disturbance; Trouble sleeping","HPO_Name__c":"Sleep disturbance","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001332","HPO_Synonym__c":"Dystonic movements","HPO_Name__c":"Dystonia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001252","HPO_Synonym__c":"Low muscle tone; Low or weak muscle tone; Muscle hypotonia; Muscular hypotonia","HPO_Name__c":"Hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Excessive production of saliva.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003781","HPO_Synonym__c":"Excessive production of saliva; Excessive salivation; Hypersalivation; Mouth watering; Oversalivation; Ptyalism; Watery mouth","HPO_Name__c":"Excessive salivation","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A degree of language development that is significantly below the norm for a child of a specified age.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000750","HPO_Synonym__c":"Deficiency of speech development; Delayed language development; Delayed speech; Delayed speech acquisition; Delayed speech and language development; Delayed speech development; Impaired speech and language development; Impaired speech development; Language delay; Language delayed; Language development deficit; Late-onset speech development; Poor language development; Speech and language delay; Speech and language difficulties; Speech delay","HPO_Name__c":"Delayed speech and language development","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Head circumference below 2 standard deviations below the mean for age and sex.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000252","HPO_Synonym__c":"Abnormally small cranium; Abnormally small skull; Decreased circumference of cranium; Decreased size of cranium; Decreased size of skull; Reduced head circumference; small cranium; Small head circumference","HPO_Name__c":"Microcephaly","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An acute dystonic reaction with blepharospasm, periorbital twitches, and protracted fixed staring episodes. There may be a maximal upward deviation of the eyes in the sustained fashion. Oculogyric crisis can be triggered by a number of factors including neuroleptic medications.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010553","HPO_Name__c":"Oculogyric crisis","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The amount of a nitrogen compound in the urine, normalized for urine concentration, is outside of normal limits.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0040416","HPO_Name__c":"Abnormal urinary nitrogen compound level","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The presence of calcium deposition affecting one or more structures of the basal ganglia.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002135","HPO_Synonym__c":"Basal ganglia calcifications; Basal ganglion calcification; Calcification of the basal ganglia","HPO_Name__c":"Basal ganglia calcification","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:238583","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Concentration of a catecholamine in the blood circulation below the lower limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:6000482","HPO_Name__c":"Decreased circulating catecholamine concentration","Feature_System__c":"Endocrine System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism"],"Disease Category":["Genetics","Neurology","Inborn Errors of Metabolism"],"Specialist":["Genetics","Neurology","Pediatrics"]},"synonyms":["bh4-deficient hyperphenylalaninemia"," deficiency of tetrahydrobiopterin"," hyperphenylalaninemia due to bh4 (tetrahydrobiopterin) deficiency"," hyperphenylalaninemia due to bh4 deficiency"," non-phenylketonuric hyperphenylalaninemia"," tetrahydrobiopterin deficiency"," tetrahydrobiopterin synthesis defect"]}