Phenylketonuria (Phenylalanine) |
Phenylalanine-4-hydroxylase (PAH) |
Neurologic impairments, with physical, cognitive, and behavioral consequences, even in well-controlled PKU |
Restriction of dietary phenylalanine. Phe-free medical formula. Sapropterin (BH4) supplementation in responsive patients. Large neutral amino acids (LNAA) |
Regier and Greene, 2000Regier DS and Greene CL (2000) Phenylalanine Hydroxylase Deficiency. 2000 Jan 10 [Updated 2017 Jan 5]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1504/ (November 01, 2017). https://www.ncbi.nlm.nih.gov/books/NBK15...
; OMIM #261600 |
Tyrosinemia type I (Tyrosine, maleylacetoacetate, fumarylacetoacetate, and succinylacetone) |
Fumarylacetoacetate hydrolase (FAH) |
Hepatomegaly, acute liver failure, cirrhosis and hepatocellular carcinoma Episodic paralysis and episodic peripheral neuropathy Renal Fanconi syndrome, renal failure, glomerulosclerosis, nephromegaly, nephrocalcinosis Gastrointestinal bleeding, paralytic ileus Pancreatic islet-cell hypertrophy, splenomegaly Rickets, chronic weakness |
Dietary management with reduced intake of phenylalanine and tyrosine; Nitisinone Liver transplantation |
Das, 2017Das AM (2017) Clinical utility of nitisinone for the treatment of hereditary tyrosinemia type-1 (HT-1). Appl Clin Genet 10:43–48.; Sniderman et al., 2006Sniderman King L, Trahms C and Scott CR (2006) Tyrosinemia Type I. 2006 Jul 24 [Updated 2017 May 25]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1515/ (November 01, 2017). https://www.ncbi.nlm.nih.gov/books/NBK15...
; OMIM #276700 |
Urea cycle disorders (Ammonia) |
Carbamoylphosphate synthetase I (CPS1); Ornithine transcarbamylase deficiency (OTC); Argininosuccinate Synthase 1 (ASS1); Argininosuccinate lyase (ASL), Arginase-1 (ARG1); N-acetylglutamate synthase (NAGS); Ornithine transporter (SLC25A15); or citrin (SLC25A13) |
Vomiting, lethargy, and behavioral abnormalities. Neurologic impairments. Seizures in acute hyperammonemia. Liver impairments |
Dietary management with reduced intake of proteins, Essential amino acids supplementation. Vitamin and mineral supplementation, Medications to increase the nitrogen excretion. Liver transplantation, |
Ah Mew et al., 2003Ah Mew N, Simpson KL, Gropman AL, Brendan ML, Lanpher C, Chapman KA and Summar ML (2003) Urea Cycle Disorders Overview. 2003 Apr 29 [Updated 2017 Jun 22]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1217/ (November 01, 2017). https://www.ncbi.nlm.nih.gov/books/NBK12...
; Häberle et al., 2012Häberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, Karall D, Martinelli D, Crespo PS, Santer R, et al. (2012) Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis 7:32.. |
Alkaptonuria (Homogentisic acid and its oxidation products) |
Homogentisate 1, 2-dioxygenase (HGD) |
Urine that turns dark on standing, alkalinization, black ochronotic pigmentation of cartilage and collagenous tissues, arthritis (especially in the spine). Cardiovascular impairments: Aortic and/or mitral valve calcification, coronary artery calcification, aortic dilatation. Urolithiasis, ochronotic prostate stones (in males) |
Nitisinone
|
Introne and Gahl, 2003Introne WJ and Gahl WA (2003) Alkaptonuria. 2003 May 9 [Updated 2016 May 12]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1454/ (November 01, 2017). https://www.ncbi.nlm.nih.gov/books/NBK14...
; Mistry et al., 2013Mistry JB, Bukhari M and Taylor AM (2013) Alkaptonuria. Rare Dis 1:e27475.; OMIMOnline Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/OMIM (July 20, 2017) http://www.ncbi.nlm.nih.gov/OMIM...
#203500 |
Propionic acidemia (Propionic acid) |
Propionyl-CoA carboxylase (PCC) |
Central nervous system impairments: acute encephalopathy, lethargy, axial hypotonia, limb hypertonia, coma, seizure, psychomotor retardation, cerebral atrophy, dystonia, cerebellar hemorrhage (rare), ischemic stroke in the basal ganglia (rare). Decreased appetite, feeding difficulties, vomiting, dehydration. Hepatomegaly, pancreatitis. Pancytopenia, neutropenia, anemia, thrombocytopenia. Cardiomyopathy, tachypnea, apnea. Osteoporosis, dermatitis acidemica |
L-carnitine, Antibiotics, Low-protein diet, Vitamin and mineral supplementation, Precursor-free amino acid and/or isoleucine/ valine supplementation. |
Baumgartner et al., 2014Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, Huemer M, Hochuli M, Assoun M, Ballhausen D, et al. (2014) Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis 9:130.; OMIM #606054https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180313/
|
Methylmalonic Acidemia (Methylmalonic acid) |
Methylmalonyl-CoA mutase (MUT) |
Central nervous system impairments: lethargy, hypotonia, developmental delay, coma, severe involvement of globus pallidus, delay in myelination, cerebellar hemorrhage (rare), ischemic stroke in the basal ganglia (rare)}. Leukopenia, thrombocytopenia. Cardiomyopathy, hepatomegaly, pancreatitis, recurrent episodes of vomiting, interstitial nephritis, chronic renal failure |
Same as in PA, plus vitamin B12 in responsive patients. |
Baumgartner et al., 2014Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, Huemer M, Hochuli M, Assoun M, Ballhausen D, et al. (2014) Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis 9:130.; OMIM #251000 |
Hemochromatosis type 1 (Iron) |
HFE protein, Hemochromatosis gene (HFE1) |
Heart involvement: cardiomyopathy, congestive heart failure, arrhythmia, cardiomegaly. Liver involvement: cirrhosis, hepatomegaly, hepatocellular carcinoma. Diabetes mellitus. Arthritis. Hypogonadotropic hypogonadism. The severe effects of the disease usually do not appear until after decades of progressive iron loading |
Periodic phlebotomy |
Seckington and Powell, 2000Seckington R and Powell L (2000) HFE-Associated Hereditary Hemochromatosis. 2000 Apr 3 [Updated 2015 Sep 17]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1440 (November 01, 2017) https://www.ncbi.nlm.nih.gov/books/NBK14...
; OMIM #235200 |
Trimethylaminuria (Amino-trimethylamine) |
Flavin-containing monooxygenase 3 (FMO3) |
Behavioral/psychiatric manifestations: depression, suicidal, psychosocial problems in school. In some patients: anemia, neutropenia, pulmonary infections; tachycardia and severe hypertension after eating cheese. |
Dietary restriction of: Trimethylamine and its precursors including choline and lecithin Trimethylamine N-oxide; Inhibitors of FMO3 enzyme activity, such as indoles. Use of: acid soaps and body lotions, activated charcoal and copper chlorophyllin, antibiotics, riboflavin supplements. |
Phillips and Shephard, 2007Phillips IR and Shephard EA (2007) Primary Trimethylaminuria. 2007 Oct 8 [Updated 2015 Oct 1]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1103/ (November 01, 2017). https://www.ncbi.nlm.nih.gov/books/NBK11...
; OMIM #602079 |