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Porphobilinogen synthase deficiency

MedGen UID:
78659
Concept ID:
C0268328
Disease or Syndrome
Synonyms: ALAD DEFICIENCY; DELTA-AMINOLEVULINATE DEHYDRATASE DEFICIENCY; DOSS PORPHYRIA; Porphyria due to ALA dehydratase deficiency; Porphyria, acute hepatic; PORPHYRIA, ALAD
SNOMED CT: Porphobilinogen synthase deficiency (64081000); ALA dehydratase deficiency porphyria (64081000); ALAD deficiency (64081000); ALADH deficiency (64081000); delta-Aminolevulinate dehydrase deficiency (64081000); Hereditary delta-aminolevulinic aciduria (64081000); delta-Aminolevulinic acid dehydratase deficiency (64081000); Acute hepatic porphyria (64081000); ALA - Aminolevulinic acid dehydratase deficiency porphyria (64081000); Delta-aminolevulinate dehydrase deficiency (64081000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ALAD (9q32)
 
Monarch Initiative: MONDO:0013000
OMIM®: 612740
Orphanet: ORPHA100924

Definition

ALAD porphyria is a rare autosomal recessive disorder that has been reported and confirmed by genetic analysis in only 5 patients (Jaffe and Stith, 2007). [from OMIM]

Clinical features

From HPO
Abdominal colic
MedGen UID:
68563
Concept ID:
C0232488
Finding
A type of abdominal pain that comes and goes in waves, most often starting and ending suddenly and being of severe intensity.
Elevated urinary delta-aminolevulinic acid
MedGen UID:
341286
Concept ID:
C1848702
Finding
An increased concentration of 5-aminolevulinic acid (CHEBI:17549) in the urine.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Paresthesia
MedGen UID:
14619
Concept ID:
C0030554
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Paralysis
MedGen UID:
105510
Concept ID:
C0522224
Finding
Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Motor paralysis results from deficits of the upper motor neurons (corticospinal, corticobulbar, or subcorticospinal). Motor paralysis is often accompanied by an impairment in the facility of movement.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
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.
Respiratory paralysis
MedGen UID:
19748
Concept ID:
C0035232
Finding
Inability to move the muscles of respiration.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPorphobilinogen synthase deficiency
Follow this link to review classifications for Porphobilinogen synthase deficiency in Orphanet.

Professional guidelines

PubMed

Moghe A, Dickey A, Erwin A, Leaf RK, O'Brien A, Quigley JG, Thapar M, Anderson KE
Mol Genet Metab 2023 Nov;140(3):107670. Epub 2023 Jul 27 doi: 10.1016/j.ymgme.2023.107670. PMID: 37542766
Wang B, Bonkovsky HL, Lim JK, Balwani M
Gastroenterology 2023 Mar;164(3):484-491. Epub 2023 Jan 13 doi: 10.1053/j.gastro.2022.11.034. PMID: 36642627Free PMC Article
Anderson KE
Mol Genet Metab 2019 Nov;128(3):219-227. Epub 2019 Jul 5 doi: 10.1016/j.ymgme.2019.07.002. PMID: 31311713Free PMC Article

Recent clinical studies

Etiology

Sardh E, Harper P
J Intern Med 2022 May;291(5):593-610. Epub 2022 Jan 23 doi: 10.1111/joim.13443. PMID: 35067977
Syed YY
Drugs 2021 May;81(7):841-848. Epub 2021 Apr 19 doi: 10.1007/s40265-021-01511-3. PMID: 33871817
Anderson KE, Lobo R, Salazar D, Schloetter M, Spitzer G, White AL, Young RM, Bonkovsky HL, Frank EL, Mora J, Tortorelli S
Am J Med Sci 2021 Aug;362(2):113-121. Epub 2021 Apr 16 doi: 10.1016/j.amjms.2021.03.004. PMID: 33865828
Phillips JD
Mol Genet Metab 2019 Nov;128(3):164-177. Epub 2019 Apr 22 doi: 10.1016/j.ymgme.2019.04.008. PMID: 31326287Free PMC Article
Pietrangelo A
Intern Emerg Med 2010 Oct;5 Suppl 1:S65-71. doi: 10.1007/s11739-010-0452-z. PMID: 20865477

Diagnosis

Jaramillo-Calle DA, Martinez YA, Balwani M, Fernandez C, Toro M
Mol Genet Metab 2021 Jul;133(3):242-249. Epub 2021 May 7 doi: 10.1016/j.ymgme.2021.04.008. PMID: 34083144
Gandhi Mehta RK, Caress JB, Rudnick SR, Bonkovsky HL
Muscle Nerve 2021 Aug;64(2):140-152. Epub 2021 Mar 31 doi: 10.1002/mus.27232. PMID: 33786855
Anderson KE
Mol Genet Metab 2019 Nov;128(3):219-227. Epub 2019 Jul 5 doi: 10.1016/j.ymgme.2019.07.002. PMID: 31311713Free PMC Article
Lin CS, Park SB, Krishnan AV
Handb Clin Neurol 2013;115:613-27. doi: 10.1016/B978-0-444-52902-2.00036-9. PMID: 23931806
Sassa S
Semin Liver Dis 1998;18(1):95-101. doi: 10.1055/s-2007-1007145. PMID: 9516683

Therapy

Wang B, Ventura P, Takase KI, Thapar M, Cassiman D, Kubisch I, Liu S, Sweetser MT, Balwani M
Orphanet J Rare Dis 2022 Aug 26;17(1):327. doi: 10.1186/s13023-022-02463-x. PMID: 36028858Free PMC Article
Sardh E, Harper P
J Intern Med 2022 May;291(5):593-610. Epub 2022 Jan 23 doi: 10.1111/joim.13443. PMID: 35067977
Scott LJ
Drugs 2020 Feb;80(3):335-339. doi: 10.1007/s40265-020-01269-0. PMID: 32034693
Anderson KE
Mol Genet Metab 2019 Nov;128(3):219-227. Epub 2019 Jul 5 doi: 10.1016/j.ymgme.2019.07.002. PMID: 31311713Free PMC Article
Kooijman MM, Brand HS
Int Dent J 2005 Apr;55(2):61-6. doi: 10.1111/j.1875-595x.2005.tb00035.x. PMID: 15880959

Prognosis

Sardh E, Harper P
J Intern Med 2022 May;291(5):593-610. Epub 2022 Jan 23 doi: 10.1111/joim.13443. PMID: 35067977
Vassiliou D, Sardh E
J Intern Med 2022 Jan;291(1):81-94. Epub 2021 Sep 23 doi: 10.1111/joim.13376. PMID: 34411356
Lahiji AP, Anderson KE, Chan A, Simon A, Desnick RJ, Ramanujam VMS
Mol Genet Metab 2020 Dec;131(4):418-423. Epub 2020 Oct 26 doi: 10.1016/j.ymgme.2020.10.011. PMID: 33199206
Yasuda M, Chen B, Desnick RJ
Mol Genet Metab 2019 Nov;128(3):320-331. Epub 2018 Nov 30 doi: 10.1016/j.ymgme.2018.11.012. PMID: 30594473Free PMC Article
Bonkowsky HL, Schady W
Semin Liver Dis 1982 May;2(2):108-24. doi: 10.1055/s-2008-1040701. PMID: 6753161

Clinical prediction guides

Wang B, Ventura P, Takase KI, Thapar M, Cassiman D, Kubisch I, Liu S, Sweetser MT, Balwani M
Orphanet J Rare Dis 2022 Aug 26;17(1):327. doi: 10.1186/s13023-022-02463-x. PMID: 36028858Free PMC Article
Farrell CP, Nicolas G, Desnick RJ, Parker CJ, Lamoril J, Gouya L, Karim Z, Tchernitchko D, Chan B, Puy H, Phillips JD
Blood Adv 2022 Feb 8;6(3):760-766. doi: 10.1182/bloodadvances.2021005484. PMID: 34724702Free PMC Article
Vassiliou D, Sardh E
J Intern Med 2022 Jan;291(1):81-94. Epub 2021 Sep 23 doi: 10.1111/joim.13376. PMID: 34411356
Phillips JD
Mol Genet Metab 2019 Nov;128(3):164-177. Epub 2019 Apr 22 doi: 10.1016/j.ymgme.2019.04.008. PMID: 31326287Free PMC Article
Yasuda M, Chen B, Desnick RJ
Mol Genet Metab 2019 Nov;128(3):320-331. Epub 2018 Nov 30 doi: 10.1016/j.ymgme.2018.11.012. PMID: 30594473Free PMC Article

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