Outcomes of mitochondrial long chain fatty acid oxidation and carnitine defects from a single center metabolic genetics clinic

Ambrose, Anastasia; Sheehan, Melissa; Bahl, Shalini; Athey, Taryn; Ghai-Jain, Shailly; Chan, Alicia; Mercimek-Andrews, Saadet

doi:10.1186/s13023-022-02512-5

Orphanet Journal of Rare Diseases

Table 2 Clinical, biochemical and molecular genetic features of AsymX patients are summarized in Table 2

From: Outcomes of mitochondrial long chain fatty acid oxidation and carnitine defects from a single center metabolic genetics clinic

Patient #/study ID/sex/diagnosis/age of diagnosis/current age	Presenting symptom (age of onset)/other clinical features	Initial investigations AC^1,2,3/TC^1,2,3/FC^1,2,3/UOA/TRR%	Molecular genetic investigations	Outcome
1/2/M/CPT-I deficiency/neonatal/3yrs	No	N/NP/75.4/↑3-HIVA /NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	Normal
2/5/F/CPT-I deficiency/6yrs/26yrs	No	NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	Normal
3/8/M/CPT-I deficiency/45yrs/53yrs	No	NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	Normal
4/9/F/CPT-I deficiency/neonatal/6yrs	No	N/N/117.75/NP/NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	Normal echo (4yrs)
5/11/F/CPT-I deficiency/39yrs/48yrs	No	NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	Normal
6/12/F/CPT-I deficiency/neonatal/2yrs	No	N/66.9/51.3/N/NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	atrial septal aneurysm, PFO, ASD, PDA (1mo)
7/50/F/CPT-I deficiency/2yrs/3yrs	No	NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	Normal
8/51/M/CPT-I deficiency/neonatal/5yrs	No	NP	HMZ c.1436C > T (p.Pro479Leu) in CPTIA	Normal
9/18/M/CTD deficiency/neonatal/7yrs	No	NP/NP/NP/NP/NP	HMZ c.769C > T (p.Arg257Trp) in SLC22A5	Normal echo (5yrs)
10/19/F/CTD deficiency/32yrs/37yrs	No	NP/2.2/1.7/N/90.88	HMZ c.845G > A (p.Arg282Gln) in SLC22A5	Normal
11/24/M/CTD deficiency/neonatal/3yrs	No	N/6.4/4.2/N/NP	HMZ c.845G > A (p.Arg282Gln) in SLC22A5	Hospital admissions (n = 2), normal echo (2yrs)
12/25/M/CTD deficiency/neonatal/3mo	No	NP/6.1/4.8/N/NP	HMZ c.845G > A (p.Arg282Gln) in SLC22A5	Normal
13/22/F/CTD deficiency/38yrs/44yrs	No/ fatigue (retrospectively at the time of diagnosis)	NP/ < 2/ < 2/NP/NP	HMZ c.248G > T (p.Arg83Leu) in SLC22A5	Normal echo (42yrs)
14/23/F/CTD deficiency/28yrs/40yrs	No/ fatigue (retrospectively at the time of diagnosis)	NP/ < 2/ < 2/NP/NP	NP	Normal echo (30yrs)
15/28/M/CTD deficiency/neonatal/6yrs	No	N/10.6/8.4/NP/NP	CMP HTZ c.1463G > A (p.Arg488His)/c.424G > T (p.Ala142Ser)/c.136C > T (p.Pro46Ser) in SLC22A5	Normal echo (5yrs)
16/32/F/CTD deficiency/26yrs/33yrs	No/ fatigue (retrospectively at the time of diagnosis)	NP/10.1/5.1/N/NP	CMP HTZ c.364G > T (p.Asp122Tyr)/ c.505C > T (p.Arg169Trp) in SLC22A5	Normal echo (27yrs)
17/36/M/CTD deficiency/neonatal/9yrs	No/ myalgia (8yrs)	NP/NP/NP/NP/NP	CMP HTZ c.424G > T (p.Ala142Ser) /c.1463G > A (p.Arg488His) /c.1324GC_1325AT (p.Ala442Ile) in SLC22A5	Normal echo (6yrs)
18/38/M/LCHAD deficiency/neonatal/6yrs	No/ RM (2yrs), retinopathy, myopathy (6 yrs)	C16OH = 0.73, C18OH = 0.87, C18:1OH = 0.54/N/N/N/NP	HMZ c.1528G > C (p.Glu474Gln) in HADHA	Hospital admissions (n = 6), normal echo (6yrs)
19/39/F/LCHAD deficiency/neonatal/3yrs	No/RM, myopathy	C16OH = 1.05, C18OH = 0.91, C18:1OH = 1.1/N/NP/NP/NP	HMZc.1528G > C (p.Glu474Gln) in HADHA	Hospital admissions (n = 4), normal echo (3yrs)
20/53/M/LCHAD deficiency/neonatal/7mo	Hypoglycemia (neonatal, but diagnosed prenatally)	C16:1OH = 0.33, C16OH = 0.78, C18:1OH = 0.45, C18OH = 0.40/N/N/N/NP	HMZ c.1528G > C (p.Glu474Gln) in HADHA	Hospital admissions (n = 2), normal echo (12yrs)
21/40/F/VLCAD deficiency/neonatal/7yrs	No/ RM, myopathy (3 yrs)	C14:1 = 0.13, C14:2 = 0.06/N/N/NP/NP	CMP HTZ c.1375dupC (p. p.Arg459ProfsX4)/c.1700G > A (p.Arg567Gln) in ACADVL	Hospital admissions (n = 1), dilated ascending aorta in echo (6yrs)
22/43/F/VLCAD deficiency/neonatal/12yrs	No/RM, myalgia (12 yrs)	N/N/N/↑AA, SUA, SEA/NP	CMP HTZ c.848 T > C (p.Val283Ala)/ c.1375dupC (p.Arg459ProfsX4) in ACADVL	Hospital admissions (n = 1)
23/44/F/VLCAD deficiency/neonatal/9yrs	No/ myalgia (4yrs)	N/N/N/NP/NP	CMP HTZ c.779C > T (p.Thr260Met/ c.1733 T > C (p.Met578Thr) in ACADVL	Hospital admissions (n = 3), normal echo (7yrs)
24/46/F/CACT deficiency/4yrs/8yrs	No	C16 = 0.85, C18:1 = 0.83, C18:2 = 0.25/N/ 14.9/NP/NP	CMP HTZ c.897dupC (p.Asn300Glnfs24)/c.269 T > G (p.Phe90Cys) in SLC25A20*	PDA in echo (6mo)

Reference Ranges: Free carnitine¹ 7.3–30.4; Free carnitine² 18.6–55.0; Free carnitine³ 25.3–57.0; Total carnitine¹ 14.0–47.0; Total carnitine² 24.9–72.1; Total carnitine³ 32.5–73.6; C16¹ 0.04–0.41; C16² 0.03–0.22; C16³ 0.03–0.19; C16-DC¹ < 0.06; C16-DC² < 0.03; C16-DC³ 0.03–0.09; C16-OH¹ < 0.05; C16-OH² < 0.04; C16-OH³ < 0.02; C18:1¹ 0.04–0.20; C18:1² 0.03–0.23; C18:1³ 0.03–0.26; C18:2¹ < 0.10; C18:2² < 0.12; C18:2³ < 0.13; C18-OH¹ < 0.03; C18-OH² < 0.03; C18-OH³ < 0.02; C18:1OH¹ < 0.02; C18:1OH² < 0.03; C18:1OH³ < 0.02; C16:1OH¹ < 0.27; C16:1OH² < 0.11; C16:1OH³ < 0.03; C14:1¹ < 0.26; C14:1² < 0.28; C14:1³ < 0.11; C14:2¹ < 0.10; C14:2² < 0.13; C14:2³ < 0.11
¹ Indicates reference range for age group newborn-2 months
² Indicates reference ranges for age group 2 months-6 years
³ Indicates reference ranges for age group 18 years and up
3-HIVA 3-OH-isovaleric acid; AA adipic acid; AC acylcarnitines; ASD atrial septal defect; CACT carnitine acylcarnitine translocase; Car carnitine; CPT-I carnitine palmitoyltransferase I; CPT-II carnitine palmitoyltransferase II; CMP HTZ compound heterozygous; CTD carnitine transporter defect; Echo echocardiography; FC free carnitine; F female; HMZ homozygous; LCHAD long-chain 3-hydroxyacyl-CoA dehydrogenase; MAD multiple acyl-CoA dehydrogenase; mo months; NB newborn; N normal; NP not performed; NR not reported; PDA patent ductus arteriosus; PFO patent foramen ovale; RM rhabdomyolysis; SEA sebacic acid; SUA suberic acid; TRR tubular reabsorption rate; UOA urine organic acids; yrs year(s); VLCAD very long-chain acyl-CoA dehydrogenase

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ISSN: 1750-1172

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