Article Figures & Data
Figures
- FIGURE 1
Diagnostic process and care planning. Metabolic test 1: blood homocysteine, acylcarnitine profile, amino acids; and, urine organic acids, glycosaminoglycans, oligosaccharides, purines, pyrimidines, GAA/creatine metabolites. Metabolic test 2 based on clinical signs and symptoms. FH, family history; MH, medical history; NE, neurologic examination; PE, physical and dysmorphology examination.
Tables
- TABLE 1
The Purposes of the Comprehensive Medical Genetics Evaluation of the Young Child With GDD or ID
1. Clarification of etiology 2. Provision of prognosis or expected clinical course 3. Discussion of genetic mechanism(s) and recurrence risks 4. Refined treatment options 5. Avoidance of unnecessary or redundant diagnostic tests 6. Information regarding treatment, symptom management, or surveillance for known complications 7. Provision of condition-specific family support 8. Access to research treatment protocols 9. Opportunity for comanagement of appropriate patients in the context of a medical home to ensure the best health, social, and health care services satisfaction outcomes for the child and family Specimena Test Notes Blood Amino acids See Table 3 Homocysteine Acylcarnitine profile Urine Organic acids GAA/creatine metabolites Purines and pyrimidines Mucopolysaccharide screen Oligosaccharide screen See Fig 1.
↵a Serum lead, thyroid function studies not included as “metabolic tests” and to be ordered per clinician judgment.
PAAs P-HCY Acylcarn UOA UPP UGAA/Cr UMPS UOligo Argininosuccinic aciduriaa Cobalamin C deficiency Cobalamin C deficiency β-ketothiolase deficiency Pyrimidine 5′nucleotidase superactivity AGAT deficiency Hurler α-mannosidosis Citrullinemiaa Cobalamin D deficiency Cobalamin D deficiency Cobalamin A deficiency Molybdenum cofactor type A deficiency GAMT deficiency Hunter Aspartylglucosaminuria Citrullinemia, type IIa Cobalamin F deficiency Cobalamin F deficiency Cobalamin B deficiency Creatine transporter defect Sanfilippo A, B, C CPS deficiencya Cobalamin E deficiency Ethylmalonic encephalopathy Cobalamin C deficiency Sly (MPS VI) Argininemiaa Cobalamin G deficiency Isovaleric acidemiaa Cobalamin D deficiency HHH syndrome MTHFR deficiencya 3-methylcrotonyl glycinuria Cobalamin F deficiency Maple syrup urine disease, variant Homocystinuria PPAa Ethylmalonic encephalopathy NAGS deficiencya Tyrosinemia, type II GA, type I MTHFR deficiencya GA, type II OTC deficiencya HMG-CoA Lyase deficiency PKU Holocarboxylase synthetase deficiency PDH complex deficiency Homocystinuria Tyrosinemia, type II Isovaleric acidemiaa 3-methylcrotonyl glycinuria 3-methylglutaconic aciduria MMAa MHBD deficiency PPAa SCOT deficiency SSADH deficiency Tyrosinemia, type II Adapted from van Karnebeek and Stockler.41
Acylcarn, acylcarnitine profile; CPS, carbamyl phosphate synthetase; GA, glutaric acidemia; HHH, hyperornithinemia-hyperammonemia-homocitrullinuria; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; MHBD, 2-methyl-3-hydroxybutyryl CoA dehydrogenase; MMA, methylmalonic acidemia; MTHFR, methylenetetrahydrofolate reductase; NAGS, N-acetylglutamate synthase; OTC, ornithine transcarbamylase; PAA, plasma amino acids; PDH, pyruvate dehydrogenase; P-HCY, plasma homocysteine; PKU; phenylketonuria; PPA, propionic acid; SCOT, succinyl-CoA:3-ketoacid CoA transferase; SSADH, succinic semialdehyde dehydrogenase; UGAA/creat; urine guanidino acid/creatine metabolites; UMPS, urine mucopolysaccharides qualitative screen (glycosaminoglycans); UOA, urine organic acids; UOGS, urine oligosaccharides; UPP, urine purines and pyrimidines.
↵a Late-onset form of condition listed; some conditions are identified by more than 1 metabolic test.
Syndrome Common Manifestations Gene, Location Aarskog syndrome Short stature, hypertelorism, downslanting palpebral fissures, joint hyperextensibility, shawl scrotum FGD1, Xp11.21 Adrenoleukodystrophy Variable and progressive vision and hearing loss, spasticity, neurological deterioration associated with demyelination of the central nervous system and adrenal insufficiency ABCD1, Xq28 Aicardi syndrome Agenesis of the corpus callosum, lacunar chorioretinopathy, costovertebral anomalies, seizures in females _____, Xp22 Allan–Herndon syndrome Generalized muscle hypoplasia, childhood hypotonia, ataxia, athetosis, dysarthria, progressing to spastic paraplegia MCT8 (SLC16A2), Xq13 ARX-related syndromes (includes Partington, Proud, West, XLAG syndromes and nonsyndromal XLMR) Partington: dysarthria, dystonia, hyperreflexia, seizures. West: infantile spasms, hypsarrhythmia. Proud: microcephaly, ACC, spasticity, seizures, ataxia, genital anomalies. XLAG: lissencephaly, seizures, genital anomalies ARX, Xp22.3 ATRX syndrome (includes ARTX, Chudley–Lowry, Carpenter–Waziri, Holmes–Gang, and Martinez spastic paraplegia syndromes and nonsyndromal XLMR) Short stature, microcephaly, hypotonic facies with hypertelorism, small nose, open mouth and prominent lips, brachydactyly, genital anomalies, hypotonia, in some cases hemoglobin H inclusions in erythrocytes XNP, (XH2) Xq13.3 Christianson syndrome Short stature, microcephaly, long narrow face, large ears, long straight nose, prominent mandible, general asthenia, narrow chest, long thin digits, adducted thumbs, contractures, seizures, autistic features, truncal ataxia, ophthalmoplegia, mutism, incontinence, hypoplasia of the cerebellum, and brain stem SLC9A6, Xq26 Coffin–Lowry syndrome Short stature, distinctive facies, large soft hands, hypotonia, joint hyperextensibility, skeletal changes RSK2, Xp22 Creatine transporter deficiency Nondysmorphic, autistic, possibly progressive SLC6A8, Xq28 Duchenne muscular dystrophy Pseudohypertrophic muscular dystrophy DMD, Xp21.3 Fragile X syndrome Prominent forehead, long face, recessed midface, large ears, prominent mandible, macroorchidism FMR1, Xq27.3 Hunter syndrome Progressive coarsening of face, thick skin, cardiac valve disease, joint stiffening, dysostosis multiplex IDS, Xq28 Incontinentia pigmenti Sequence of cutaneous blistering, verrucous thickening, and irregular pigmentation. May have associated CNS, ocular abnormalities NEMO (IKB6KG), Xq28 Lesch–Nyhan syndrome Choreoathetosis, spasticity, seizures, self-mutilation, uric acid urinary stones HPRT, Xq26 Lowe syndrome Short stature, cataracts, hypotonia, renal tubular dysfunction OCRL, Xq26.1 MECP2 duplication syndrome Hypotonia, progressing to spastic paraplegia, recurrent infections MECP2, Xq28 Menkes syndrome Growth deficiency, full cheeks, sparse kinky hair, metaphyseal changes, limited spontaneous movement, hypertonicity, seizures, hypothermia, lethargy, arterial tortuosity, death in early childhood ATP7A, Xpl3.3 Pelizaeus–Merzbacher disease Nystagmus, truncal hypotonia, progressive spastic paraplegia, ataxia, dystonia PLP, Xq21.1 Renpenning syndrome (includes Sutherland–Haan, cerebropalatocardiac, Golabi–Ito–Hall, Porteous syndrome Short stature, microcephaly, small testes. May have ocular or genital abnormalities PQBP1, Xp11.3 Rett syndrome XLMR in girls, cessation and regression of development in early childhood, truncal ataxia, autistic features, acquired microcephaly MECP2, Xq28 X-linked hydrocephaly-MASA spectrum Hydrocephalus, adducted thumbs, spastic paraplegia L1CAM, Xq28 Reproduced with permission from Stevenson and Schwartz.46
In this issue
Comprehensive Evaluation of the Child With Intellectual Disability or Global Developmental Delays
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- Boys With Suspected or Known XLID
- Female Gender and MECP2 Testing
- Advances in Diagnostic Imaging
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